Metformin overdose
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Metformin Overdose: Clinical Manifestations and Management
Introduction to Metformin Overdose
Metformin, a widely used oral antihyperglycemic agent for type 2 diabetes, can lead to severe and potentially fatal complications when overdosed. The primary concern in metformin overdose is the development of lactic acidosis, a condition characterized by an elevated lactate level and metabolic acidosis. This article synthesizes findings from multiple studies to provide a comprehensive overview of the clinical manifestations, risk factors, and management strategies for metformin overdose.
Clinical Manifestations of Metformin Overdose
Metabolic Acidosis and Hyperlactatemia
Metformin overdose frequently results in metabolic acidosis with hyperlactatemia. Patients often present with severe lactic acidosis, characterized by low serum pH and high lactate levels. For instance, a study reported that patients with a nadir serum pH less than 6.9 had an 83% mortality rate, and those with lactate concentrations greater than 25 mmol/L also had an 83% mortality rate. Another case highlighted a patient with a serum pH of 6.83 and lactate level of 24 mmol/L, which worsened despite continuous venovenous hemofiltration (CVVHDF).
Renal and Cardiovascular Complications
Acute renal insufficiency is a common complication in metformin overdose, often exacerbating the drug's toxicity due to impaired clearance. A case report described a patient with acute renal insufficiency, severe lactic acidosis, and rapidly progressive hyperglycemia, who ultimately succumbed despite aggressive treatment. Cardiovascular instability, including shock and cardiac arrest, is also frequently observed .
Neurological and Respiratory Effects
Neurological symptoms such as obtunded mental status and hypoglycemic encephalopathy can occur. A 14-year-old girl developed hypoglycemic encephalopathy following a metformin overdose, leading to severe brain dysfunction and coma. Respiratory complications, including acute respiratory distress syndrome (ARDS) and hypoxemic respiratory failure, have also been reported.
Risk Factors and Prognostic Indicators
Serum pH, Lactate, and Metformin Concentrations
The severity of metabolic acidosis, as indicated by serum pH and lactate levels, is a critical prognostic indicator. Survivors of metformin overdose typically have higher nadir serum pH and lower peak lactate levels compared to nonsurvivors. Additionally, peak serum metformin concentrations are significantly higher in nonsurvivors, with levels exceeding 50 µg/mL associated with increased mortality.
Underlying Health Conditions
Patients with pre-existing renal impairment are at higher risk of severe outcomes due to reduced metformin clearance. A case involving a 70-year-old woman with diabetes and impaired renal function highlighted the fatal consequences of metformin intoxication in such patients.
Management Strategies for Metformin Overdose
Initial Stabilization and Supportive Care
Early recognition and intensive supportive care are crucial. Initial management includes stabilizing the cardiovascular system, correcting metabolic acidosis, and maintaining body temperature. Sodium bicarbonate infusion is commonly used to manage acidosis, although its efficacy may be limited in severe cases.
Extracorporeal Treatments
Hemodialysis (IHD) and continuous renal replacement therapy (CRRT) are effective in removing metformin and correcting metabolic derangements. IHD has been shown to improve acidosis and hyperlactatemia more effectively than CVVHDF in some cases. A combination of IHD and CVVHDF, along with vasopressor support, has resulted in survival in severe overdose cases.
Advanced Interventions
In cases of severe hemodynamic instability and respiratory failure, extracorporeal membrane oxygenation (ECMO) may be necessary. ECMO has been used successfully to manage persistent acidosis and support hemodynamic stability in critical patients.
Conclusion
Metformin overdose is a medical emergency that requires prompt and aggressive management. Key prognostic indicators include serum pH, lactate levels, and metformin concentrations. Early supportive care, along with advanced interventions such as hemodialysis and ECMO, can significantly improve outcomes. Understanding the clinical manifestations and effective management strategies is essential for healthcare providers to mitigate the risks associated with metformin overdose.
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